Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Upon exposure to the bacterial chemotactic peptide fMet-Leu-Phe, human neutrophils release lysozyme and generate superoxide anions (O2.-). The synthetic lipoamino acid N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteine (Pam3Cys), which is derived from the N-terminus of bacterial lipoprotein, when attached to Ser-(Lys)4 [giving Pam3Cys-Ser-(Lys)4], activated O2.- formation and lysozyme release in human neutrophils with an effectiveness amounting to about 15% of that of fMet-Leu-Phe. Palmitic acid, muramyl dipeptide, lipopolysaccharide and the lipopeptides Pam3Cys-Ala-Gly, Pam3Cys-Ser-Gly, Pam3Cys-Ser, Pam3Cys-OMe and Pam3Cys-OH did not activate O2.- formation. Pertussis toxin, which ADP-ribosylates guanine-nucleotide-binding proteins (G-proteins) and functionally uncouples formyl peptide receptors from G-proteins, prevented activation of O2.- formation by fMet-Leu-Phe and inhibited Pam3Cys-Ser-(Lys)4-induced O2.- formation by 85%. Lipopeptide-induced exocytosis was pertussis-toxin-insensitive. O2.- formation induced by Pam3Cys-Ser-(Lys)4 and fMet-Leu-Phe was enhanced by cytochalasin B, by a phorbol ester and by a diacylglycerol kinase inhibitor. Addition of activators of adenylate cyclase and removal of extracellular Ca2+ inhibited O2.- formation by fMet-Leu-Phe and Pam3Cys-Ser-(Lys)4 to different extents. Pam3Cys-Ser-(Lys)4 synergistically enhanced fMet-Leu-Phe-induced O2.- formation and primed neutrophils to respond to the chemotactic peptide at non-stimulatory concentrations. Our data suggest the following. (1) Pam3Cys-Ser-(Lys)4 activates neutrophils through G-proteins, involving pertussis-toxin-sensitive and -insensitive processes. (2) The signal transduction pathways activated by fMet-Leu-Phe and Pam3Cys-Ser-(Lys)4 are similar but not identical. (3) In inflammatory processes, bacterial lipoproteins and chemotactic peptides may interact synergistically to activate O2.- formation, leading to enhanced bactericidal activity.
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PMID:Activation of superoxide formation and lysozyme release in human neutrophils by the synthetic lipopeptide Pam3Cys-Ser-(Lys)4. Involvement of guanine-nucleotide-binding proteins and synergism with chemotactic peptides. 216 Feb 37

Two gastrin analogs containing a D- and a L-tetrafluorinated tyrosyl residue (Arg-Arg-Leu-Glu-Glu-Glu-Glu-Glu-Ala-(F4)Tyr-Gly) were synthesized and tested as substrates and inhibitors of the insulin receptor kinase. No phosphorylation of these peptides was observed, but both gastrin analogs were effective inhibitors in the microM range. Although the D- and L-tetrafluorotyrosine-gastrin analogs differ in the sequence by only 1 amino acid residue, a different inhibitory pattern was obtained with the insulin receptor. The inhibition of all-L-isomer is competitive with respect to both the protein substrate, reduced, S-carboxymethylated, and maleylated lysozyme (RCMM-lysozyme), and ATP with a Ki value of 4 microM. This result corroborates a previous finding (Walker, D. H., Kuppuswamy, D., Visvanathan, A., and Pike, L. J. (1987) Biochemistry 26, 1428-1433) that the kinetic mechanism for insulin receptor is a random Bi Bi mechanism. Different from the L-isomer, the D-analog is competitive to RCMM-lysozyme and noncompetitive toward ATP and gives an apparent inhibition constant of 20 microM. A free tetrafluorotyrosine also shows a competitive inhibition to protein substrate, RCMM-lysozyme (Ki = 18 mM) whereas free tyrosine shows no effect on the activity of insulin receptor. These results show the importance of the charge state and nucleophilicity of the phenolic component in substrate recognition and catalysis and provide a rationale for the design of inhibitors of tyrosyl phosphorylation.
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PMID:A rationale for the design of an inhibitor of tyrosyl kinase. 216 84

The role of tyrosine kinases in the responses of human neutrophils to chemotactic factors was examined using the recently described inhibitor erbstatin. Pre-incubation with erbstatin decreased the amount of tyrosine phosphorylation induced by the formylated oligopeptide formyl-methionyl-leucyl-phenylalanine (fMet-Leu-Phe) without effecting the binding of [3H]-fMet-Leu-Phe. Erbstatin also dose-dependently inhibited the production of superoxide anion induced by fMet-Leu-Phe and platelet-activating factor, but did not affect the oxidative burst induced by either the calcium ionophore A23187 or the phorbol ester phorbol 12-myristate 13-acetate. Furthermore, erbstatin diminished the cytosolic acidification elicited by fMet-Leu-Phe, platelet-activating factor, and leukotriene B4. In contrast, erbstatin was without effect on the increase in the levels of cytoplasmic free calcium and polymerized actin elicited by fMet-Leu-Phe, C5a, leukotriene B4 and platelet-activating factor, whereas the increase in cytoplasmic free calcium elicited by platelet-derived growth factor was inhibited by erbstatin. In addition, erbstatin affected neither the release of elastase stimulated by these agonists nor the release of beta-glucosaminidase, lysozyme or vitamin B12-binding protein induced by fMet-Leu-Phe. These results indicate that tyrosine protein kinases are involved in the signaling pathways employed by chemotactic factors in the stimulation of selective functional responses (and superoxide production in particular) in human neutrophils.
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PMID:Selective inhibition of human neutrophil functional responsiveness by erbstatin, an inhibitor of tyrosine protein kinase. 217 35

Paramagnetic agents produce line broadening and thus cancellation of anti phase cross-peak components in two-dimensional correlated nuclear magnetic resonance spectra. The specificity of this effect was examined to determine its utility for identifying surface residues of proteins. Ubiquitin and hen egg white lysozyme, for which X-ray crystal structures and proton NMR assignments are available, served as test cases. Two relaxation reagents were employed, 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxy and the gadolinium (III) diethylenetriaminepentaacetate complex ion. Correlations were sought between reagent-produced decreases of side-chain cross-peak volumes in double-quantum-filtered proton correlation (DQF-COSY) spectra and the solvent-exposed side-chain surface area of the corresponding residues. The lanthanide complex produced strong effects ascribable to association with carboxylate groups but was not otherwise useful in delineating surface residues. The nitroxyl, on the other hand, produced clear distinctions among the Val, Leu, and Ile residues that generally paralleled side-chain exposure in the crystal, although consistent correlations were not observed with residues of other types. Although an instance of possible specific protein-nitroxyl association was noted, the nitroxyl appears to be a tool for identifying hydrophobic surface residues.
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PMID:NMR identification of protein surfaces using paramagnetic probes. 217 60

Histochemical and immunohistochemical studies have been reported in only a few cases of sinus histiocytosis with massive lymphadenopathy (SHML) to date. These indicate that SHML cells belong to the macrophage/histiocyte family, but their exact origin is still unknown. We determined the antigenic phenotype of SHML cells in sections from 20 cases of routinely fixed, paraffin-embedded tissue and from two cases of fresh frozen tissue using a broad panel of antibodies to macrophage/histocyte, B-, and T-cell antigens. SHML cells expressed the following: (1) S-100 protein, (2) "pan-macrophage" antigens such as EBM11, HAM 56, and Leu-M3, (3) antigens functionally associated with phagocytosis (Fc receptor for IgG, complement receptor 3), and lysosomal activity (lysozyme, alpha 1-antichymotrypsin, and alpha 1-antitrypsyn), (4) antigens associated with early inflammation (Mac-387, 27E10), (5) antigens commonly found on monocytes, but not tissue macrophages (OKM5, Leu-M1), and (6) "activation" antigens (Ki-1 and receptors for transferrin and interleukin 2). These data suggest that SHML cells are true functionally activated macrophages that may be recently derived from circulating monocytes.
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PMID:Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). 218 14

Several immunohistochemical methods are now available for the staining of neoplastic cells in tissue sections. The authors have found that the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method is sensitive and reliable. Murine monoclonal or nonmurine polyclonal antibodies can be used to label a variety of membranous and/or cellular constituents in tissues that have been routinely processed in a histopathology laboratory. The monoclonal antibody against leukocyte common antigen (CD45) can be used to differentiate hematologic from nonhematologic tumors. Monoclonal antibodies (L26, LN1, LN2, LN3, MB1, MB2) label B-cell lymphomas, whereas other monoclonal antibodies (UCHL1, MT1) more characteristically stain T-cell lymphomas. Polyclonal antibodies against CD3 specifically mark neoplastic cells from T-cell lymphomas and leukemias but as yet are not commercially available. Monoclonal antibodies Leu-M1 (CD15), Ber H2 (Ki-1; CD30), and LN2 label Reed-Sternberg cells from most cases of nodular sclerosis, mixed cellularity, and lymphocyte-depleted Hodgkin's disease. Monoclonal antibodies Mac 387, KP1 (CD68), and NP57 (antielastase), as well as polyclonal antibodies against lysozyme, help identify subtypes of acute myeloid leukemia and extramedullary myeloid cell tumors. Although there are now excellent reagents ready for use, there is still a significant need for more lineage-specific (particularly against CD epitopes) monoclonal antibodies capable of labeling neoplastic cells in paraffin-embedded tissue sections from patients with hematologic malignancies.
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PMID:Immunophenotyping of hematologic neoplasms in paraffin-embedded tissue sections. 218 Feb 77

The proton and nitrogen (15NH-H alpha-H beta) resonances of bacteriophage T4 lysozyme were assigned by 15N-aided 1H NMR. The assignments were directed from the backbone amide 1H-15N nuclei, with the heteronuclear single-multiple-quantum coherence (HSMQC) spectrum of uniformly 15N enriched protein serving as the master template for this work. The main-chain amide 1H-15N resonances and H alpha resonances were resolved and classified into 18 amino acid types by using HMQC and 15N-edited COSY measurements, respectively, of T4 lysozymes selectively enriched with one or more of alpha-15N-labeled Ala, Arg, Asn, Asp, Gly, Gln, Glu, Ile, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr, or Val. The heteronuclear spectra were complemented by proton DQF-COSY and TOCSY spectra of unlabeled protein in H2O and D2O buffers, from which the H beta resonances of many residues were identified. The NOE cross peaks to almost every amide proton were resolved in 15N-edited NOESY spectra of the selectively 15N enriched protein samples. Residue specific assignments were determined by using NOE connectivities between protons in the 15NH-H alpha-H beta spin systems of known amino acid type. Additional assignments of the aromatic proton resonances were obtained from 1H NMR spectra of unlabeled and selectively deuterated protein samples. The secondary structure of T4 lysozyme indicated from a qualitative analysis of the NOESY data is consistent with the crystallographic model of the protein.
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PMID:Assignment of the backbone 1H and 15N NMR resonances of bacteriophage T4 lysozyme. 220 79

A case of lymphocyte-depletion Hodgkin's disease is described for the purpose of reviewing the criteria currently used to distinguish this disease from other pleomorphic large-cell malignancies. A 76-year-old man with a 3-month history of daily fevers underwent extensive evaluation and exploratory laparotomy, which revealed only two large, separate splenic tumor nodules. Postoperatively, the patient remained asymptomatic. Histologically, the tumor was composed of giant cells, including both typical Reed-Sternberg forms and mononuclear variants with inflammatory stromal response along its borders. Immunoperoxidase showed tumor cells to be strongly reactive for Leu-M1 (CD15), BER-H2 (CD30), Leu-3 (CD4), and T11 (CD2) and weakly reactive for Leu-4 (CD3) but nonreactive for EMA, LCA, lysozyme, Leu-9, Leu-M3, Leu-M5, and immunoglobulin light chains. Southern blot analysis revealed an isolated clonal band for kappa light chain only. Included in the discussion of this case of primary splenic lymphocyte-depletion Hodgkin's disease is a review of clinical, histologic, immunohistochemical, and gene-rearrangement characteristics of what can be defined as lymphocyte-depletion Hodgkin's disease.
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PMID:Primary splenic lymphocyte-depletion Hodgkin's disease. 222 Jun 73

The clinical and pathological findings in a patient with monocytic aleukemic leukemia presenting initially as multiple monoblastic tumors of the skin is described. The patient was a 35-year-old Japanese woman, who had first noticed multiple, asymptomatic, reddish-brown papules on her trunk. Asymptomatic enlargements of several lymph nodes were present in the bilateral cervical and axillary areas. There was no hepatosplenomegaly, sternal tenderness, bruising, or bleeding. The skin and lymph node biopsies were originally interpreted as malignant lymphoma. The diagnosis of acute monocytic leukemia was established when bone marrow involvement was detected. Immunohistochemical observation of the skin eruptions revealed the following: Positive staining with lysozyme was noted in almost half of the infiltrating atypical cells. Most of the infiltrating cells reacted positively with antisera to Leu-M5 and some of them reacted to Leu-M1. The helper T cell antibody, Leu-3a+3b, showed weak positive staining of most infiltrating cells. However, there were no reactions with antisera to Leu-6, Leu-7, Leu-14, CALLA, OKT 6, OKT 8, OKT 16, OKB 19, OKM 14, beta F1, or delta TCS1. OKM 5-positive keratinocytes were observed in some parts of the upper epidermis, although no OKM 5 expression could be detected on any tumor cells. Cytochemistry, immunohistochemistry, and electron microscopy can aid in the diagnosis of monocytic leukemia. This case illustrates the importance of using an expanded panel of monoclonal antisera in certain hematopoietic tumors.
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PMID:Cutaneous involvement as a presenting feature of monocytic leukemia: morphological and immunohistochemical studies. 227 62

A case of localized histiocytosis X of the penis was reported. The patient was a 9-year-old boy who had several tumor lesions on the glans penis and inner layer of prepuce. Biopsy specimens were studied by H-E staining and immunohistochemical staining for S-100 protein (S-100), lysozyme (Lys), leucocyte common antigen (LCA), and Leu-M1. They revealed diffuse infiltration of many atypical histiocytes, which were shown to be S-100+, Lys+, LCA- and Leu-M1-. This indicates that these cells were derived from T-zone histiocyte system. After complete remission of these tumors, the other one arose from anal mucosa. In the literature we could find only one case of a primary penile lesion reported by Myers and others.
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PMID:[A case of histiocytosis X of the penis]. 229 25


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